Inhibition of the multifunctional homeodomain-interacting protein kinase 2 (HIPK2) alleviates thoracic aortic disease in mice with progressively severe Marfan syndrome

Thoracic aortic aneurysm (TAAs) are a severe complication in Marfan Symdrome (MFS), often leading to dissection and premature death. To identify potential drug targets for the treatment for TAAs we used gene expression profiles from MFS mice and patients to predict kinases that regulate gene expression. Among the top predictions was the kinase HIPK2. Ubiquitous post-natal inactivation of the HIPK2 gene, as well as chronic administration of an allosteric inhibitor of HIPK2/Smad3 interaction, increased the survival of MFS mice and improved multiple surrogate parameters. The data that was first published with this study, contained 4 samples obtained from both MFS and WT mice and 3 samples obtained from both MFS patients and non-MFS control subjects.胸主动脉瘤（Thoracic Aortic Aneurysm, TAAs）是马方综合征（Marfan Syndrome, MFS）的严重并发症，常引发主动脉夹层与过早死亡。为挖掘胸主动脉瘤治疗的潜在药物靶点，本研究利用马方综合征小鼠与患者的基因表达谱，预测调控基因表达的激酶。排名靠前的预测靶点之一为激酶HIPK2。对HIPK2基因进行产后全身性失活，以及长期给予HIPK2/Smad3相互作用的变构抑制剂，均可提升马方综合征小鼠的存活率，并改善多项替代指标。本研究首次发表时附带的数据集，包含4组马方综合征小鼠与野生型（Wild Type, WT）小鼠样本，以及3组马方综合征患者与非马方综合征对照受试者的样本。